The research proposed in this project is directed toward elucidating events which control beta adrenergic receptor function both at the cellular and tissue levels: (1) The question of whether a direct functional relationship exists in cell membranes between beta adrenergic receptors and calcium channels will be examined by assessing the synthesis patterns of the beta adrenergic receptor, calcium channel, and adenylate cyclase macromolecules during various stages of the cell cycle. (2) Membrane-beta receptor and calcium channel dynamics will be explored utilizing fluorescent labeled catecholamine polymers and organic calcium channel antagonists covalently coupled to polymers. Receptor density patterns and motility will be examined as function of ligand binding. Receptor crossslinking studies will be used in an attempt to determine the distance between receptors and calcium channels in the membrane. (3) Purification of cell membrane fragments "enriched" with adrenergic receptors will be attempted by utilizing affinity chromatography and affinity partitioning. (4) The tissue sites of catecholamine action in cardiac muscle will be investigated. The relationship between adrenergic receptor occupancy, increases in cyclic AMP, and initiation of cardiac inotropic responses will be examined using catecholamine covalently immobilized on soluble co-amino acid polymers of varying molecular weight. The diffusion properties of these macromolecules provide the means of testing the above parameters by relating the fractional uptake of the catecholamine to the extent of tissue activation (contractility and cyclic AMP).